NSF Award
0645794
The phenylpropanoid biosynthetic pathway of bacteria and plants allows one to study evolutionary change in enzymes and metabolic pathways underlying the emergence and rapid expansion of chemical diversity in living systems. Ultimately these studies lead to a better understanding of the chemical, structural and evolutionary tenets governing biodiversity and biocomplexity at a chemical level. Sessile organisms such as plants and microbes acquired and evolved specialized biosynthetic networks classified as secondary metabolic pathways, the output of which are regio- and stereo-chemically complex small molecule natural products including phenylpropanoid-derived metabolites. These chemicals of specialized metabolism serve as chemical languages in ecosystems and impart a species-specific chemical "signature" on the parent organism. The means by which organisms acquire, improve and exploit diverse metabolic systems to generate a rich repertoire of chemically complex natural products play key roles in the rapid expansion of many ecosystems, and therefore, hold incredible adaptive significance for the diversity of life. While seemingly insignificant, specialized metabolites often serve as key mediators of intra- and interspecies interactions resulting in speciation, survival and ecological homeostasis. Under the evolutionary restraints of chemically established adaptation, diverse molecular changes associated with specialized metabolism are often preserved genetically in a particular species' genome and are discerned at a functional and structural level. These often ecotype-specific genomes are the direct result of the increased fitness of host organisms "chemically" adapted to specific ecological niches. Therefore, these specialized metabolic pathways and their "chemical output" present us with a rich evolutionary record of where biosynthetic pathways, natural chemicals and biosynthetic enzymes have been (vestigial biochemical traits), what adaptive advantages these complex enzymatic systems hold in the present (emergent function), and ultimately where these pathways may be heading in the future (functional plasticity). The overarching goal of this research is to map the adaptive molecular changes that have occurred in the phenylpropanoid biosynthetic pathway as these enzyme networks emerged and subsequently evolved from their ancestral roots in primary metabolism billions of years ago. To accomplish these goals, the work involves a multidisciplinary approach including synthetic chemistry, protein x-ray crystallography, site-specific and combinatorial mutagenesis, kinetic assays and research using the reference plant Arabidopsis thaliana to answer unresolved, recently discovered and unexpected evolutionary aspects of the general phenylpropanoid biosynthetic pathway.<br/><br/>Broader Impacts<br/>The research activities integrate the training of high school students (San Diego area), teachers (Tucson area), undergraduate students (University of California, San Diego) and PhD level scientists in state of the art multidisciplinary research including structural biology, chemistry, biochemistry and evolutionary biology. The research fully integrates these students in the discovery process that includes co-authorship on scientific publications. Summers will involve a 9-week training program for teachers in the Tucson, Arizona area as part of a collaborative program with Dr. David Gang at the University of Arizona. The work will then be extended to the classroom during the normal school year through the preparation of protein crystallization kits for high school science classes that also incorporate protein samples chosen to potentially address fundamental questions about protein evolution in three dimensions. Given this, it is hoped that the students will become vested in the scientific method that will ultimately result in the class's co-authorship on scientific publications. Finally, at least twice yearly, the PI participates in an evening seminar series for the general public called "A Taste of Discovery". The PI's most recent presentation focused on the evolution of chemical biosynthesis in plants, why this research is critical for terrestrial life and how mankind exploits plants and plant-based chemicals for health and nutrition.
